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Today, peripheral
Pathophysiology
Peripheral anterior synechiae may form under the following 2 circumstances: a nonproliferative state or a
proliferative state.
Apposition of the iris against the trabecular meshwork as a result of pupil block or a posterior pushing
mechanism without any inflammation can result in continuous peripheral anterior synechiae. These
continuous peripheral anterior synechiae lead to "zippering" of the angle. Primary angle-closure glaucoma
and the various posterior pushing mechanisms are examples of this process.
In the presence of inflammation or cellular proliferation, a membrane forms between the iris and the
trabecular meshwork, creating the peripheral anterior synechiae. This membrane contracts, resulting in
angle-closure glaucoma by an anterior pulling mechanism. Examples of this process include the
fibrovascular membrane formed in neovascular glaucoma, proliferating abnormal endothelial cells in the
iridocorneal endothelial (ICE) syndromes, epithelialization of the angle due to epithelial ingrowth, or
inflammatory trabecular and keratic precipitates in contact with an inflamed iris. These processes can be
accentuated by iris swelling and protein transudation and exudation.
Physical
As a general principle, examination of the nonaffected eye in unilateral presentations may prove to be
valuable in trying to discern between primary and secondary etiologies of angle closure.
Gonioscopy
o
Zeiss compression
Areas where an abrupt change in the angle from open to closed is present suggest
the presence of peripheral anterior synechiae.
Has a lacy and porous appearance through which angle structures can be visualized; this
can be enhanced with transillumination
Axenfeld and Rieger anomalies (anterior segment dysgenesis) may have anterior
prominent uveal meshwork with an anterior displaced Schwalbe line, which is not
believed to be true peripheral anterior synechiae.
Cornea
o
Descemet
membrane
level
suggest
posterior
Posterior embryotoxon
If the peripheral depth in this region has a corneal thickness of one fourth or less, the
possibility of angle closure exists (Von Herrick law).
Pupil block commonly results in greater peripheral shallowing as compared to the central
anterior chamber.
Iris atrophy may suggest previous attacks of angle-closure glaucoma, uveitis, or anterior
segment dysgenesis.
New vessels along the anterior iris stroma and ectropion uveae suggest neovascular
glaucoma.
Ectropion uveae, corectopia, iris stretch holes, and nevi suggest an iridocorneal
endothelial syndrome.
Anterior bowing of the iris may imply an element of pupil block or iris bomb.
Iris
Lens
o
Retina
Any cause of vascular compromise (eg, diabetic retinopathy, central retinal artery
occlusion [CRAO], central retinal vein occlusion [CRVO]) can be a precipitant for
rubeosis.
Optic nerve
With or without cupping - May have cupping with persistent increased intraocular
pressure with optic nerve damage; if intraocular pressure is normal or near-normal, optic
nerve may not have evidence of cupping on clinical examination.
Intraocular pressure
o
Rises when a significant portion of the angle is occluded by peripheral anterior synechiae
(usually > two thirds).
Intraocular pressure may be normal even if a significant portion of the angle has been
closed by peripheral anterior synechiae due to the phenomenon of bridging, ie, when the
iris has attached anterior to the trabecular meshwork, leaving a space in front of the
trabecular meshwork allowing it to function. This typically occurs in iridocorneal
endothelial syndromes and congenital anomalies and is not seen in primary angle closure.
Causes
Table 2. Summary of Important Mechanisms and Causes of Peripheral Anterior Synechiae (Open Table in
a new window)
Iris Pulled Forward
Iris Pushed Forward
Neovascular membrane ICE membrane Posterior polymorphous Pupil block
dystrophy Epithelial/fibrous ingrowth
Uveitis
Trauma
Inflammatory syndromes
Infectious
Pseudophakic or aphakic pupil block
Lens related
Iridoschisis
Plateau iris
Posterior pushing
Postsurgical
Choroidal effusion
Trauma
-Posterior uveitis
-CRVO
-Nanophthalmos
Suprachoroidal hemorrhage
-Retinoblastoma
-Retinopathy of prematurity
Neurofibromatosis
The pars plicata is contiguous with the iris posterior surface and is approximately 2 mm in
length, 0.5 mm in width, and 0.8-1 mm in height [2,3].
Thus, the ciliary processes have a large surface area, estimated to be 6 cm2, for ultrafiltration and
active fluid transport, this being the actual site of aqueous production; the pars plicata accounts
for approximately 25% of the total length of the ciliary body (2 mm) [4] (figure 2)
The posterior portion of the ciliary body is called the pars plana or orbicularis ciliaris, which
has a relatively flat and very pigmented inner surface, and is continuous with the choroid at the
ora serrata. In the adult eye, the anterior-posterior length of the ciliary body ranges 4.5-5.2 mm
nasally and 5.6 -6.3 mm temporally [5]. The ciliary body is composed of muscle, vessels and
epithelium.
Figure 2. Pars plicata of rabbit ciliary body (courtesy of Prof. Durval Carvalho Jr.)
Ciliary muscle
The ciliary muscle consists of three separate muscle fibers: longitudinal, circular and oblique.
The longitudinal fibers (meridional), which are the most external, attach the ciliary body
anteriorly to the scleral spur and trabecular meshwork at the limbus, and posteriorly to the
supracoroidal lamina (fibers connecting choroid and sclera) as far back as the equator of the eye
[6].
The contraction of the longitudinal muscle, opens the trabecular meshwork and Schlemm`s
canal. The circular fibers (sphincteric) make up the more anterior and inner portion, and run
parallel to the limbus. This insertion is in the posterior iris. When these fibers contract, the
zonules relax, increasing the lens axial diameter and its convexity.
The oblique fibers (radial or intermediate) connect the longitudinal and circular fibers. The
contraction of these fibers may widen the uveal trabecular spaces.
Ciliary vessels
Traditional views hold that the vasculature of the ciliary body is supplied by the anterior ciliary
arteries and the long posterior ciliary arteries, forming the major arterial circle near the root of
the iris, wherefrom branches supply the iris, ciliary body and the anterior choroid. Recent studies
in primates have shown a complex vascular arrangement with collateral circulation on at least
three levels [7,8]: an episcleral circle formed by anterior ciliary branches; an intramuscular circle
formed through the anastomosis between anterior ciliary arteries and long posterior ciliary artery
branches; and the major arterial circle formed primarily, if not exclusively, by paralimbal
branches of the long posterior ciliary arteries. The major arterial circle is the immediate vascular
supply of the iris and ciliary processes [8,9].
Ciliary epithelia
The inner surfaces of the ciliary processes and the pars plana are lined by two layers of
epithelium. (figure 3.The outer layer is the pigmented epithelium, which is composed of low
cuboidal cells and is adjacent to the stroma and continuous with the retinal pigmented
epithelium. The inner layer is formed by the nonpigmented epithelium, a columnar epithelium,
adjacent to the aqueous humor in the posterior chamber and continuous with the retina. These
two layers of the epithelium are appositioned in their apical surfaces.
Innervation
The major innervation is provided by ciliary nerve branches (third cranial nerve-oculomotor),
forming a rich parasympathetic plexus. There are also sympathetic fibers originating from the
superior cervical ganglion which keep pace with arteries and their branches.
The pigmented epithelium is the outer layer, and the cuboidal cells contain numerous melanin
granules in their cytoplasm. This layer is separated from the stroma by an atypical basement
membrane, a continuation of Bruch`s membrane which contains collagen and elastic fibers [15].
The nonpigmented epithelium is composed of columnar cells with numerous mitochondria,welldeveloped endoplasmic reticulum seen in the cytoplasm, extensive infoldings of the membranes
and tight junctions between the apical cell membranes. The basement membrane faces the
aqueous humor, is composed of fibrils in a glycoprotein with laminin and collagens I, III and IV
[16]. The apical cells of this membrane are connected by tight junctions (zonulae occludentae),
creating a permeability barrier, which is an important component of the bloodaqueous barrier
called the internal limiting membrane.
Adjacent cells within each epithelial layer and between the apical cells of the two layers are
connected by gap junctions, tight junctions and desmosomes. The apical membranes of the
nonpigmented epithelium are also joined by tight junctions [12,13,14].These tight junctions are
permeable only to low-molecular-weight solutes. The anterior portion of the nonpigmented
ciliary epithelium has the morphologic features of a tissue involved in active fluid transport, i.e.,
evidence of abundant sodium-potassium adenosine triphosphatase ( Na+ K+ ATPase), glycolytic
enzymes activity, and incorporation of labeled sulfate into glycolipids and glycoproteins [17].
There are many indications that the aqueous humor is produced in the anterior portion of the
nonpigmented epithelia of ciliary processes [17,18,19].
There is a potential space between the two epithelial layers, called "ciliary channels". The
aqueous humor may be secreted into this space after beta-adrenergic agonist stimulation, but
this notion requires additional studies [20].
Anterior chamber angle
The iris inserts into the anterior side of the ciliary body and separates the aqueous compartment
into a posterior and anterior chamber. The angle formed by the iris and the cornea is the anterior
chamber angle6. The aqueous humor is formed by the ciliary process, passes from posterior
chamber to the anterior chamber through the pupil, and leaves the eye at the anterior chamber
angle. Most of the aqueous humor exits the eye through the trabecular meshwork, which is called
the conventional or canalicular system, and accounts for 83 to 96% of aqueous outflow of normal
human eyes [21,22].
The other 5-15% of the aqueous humor leaves the eye through the uveoscleral and uveovortex
systems (unconventional systems), including anterior ciliary muscle and iris to reach supraciliary
and suprachoroidal spaces [22,23,24].
Anatomy of anterior chamber angle (conventional outflow system)
a. Schwalbe`s line
This line or zone represents the transition from the trabecular to corneal endothelium, the
termination of Descemet`s membrane, and the trabecular insertion into the corneal stroma.
Schwalbe`s line is just anterior to the apical portion of the trabecular meshwork, is composed of
collagen and elastic tissue and has a width that varies 50-150 m; it has been called Zone S [25].
b. Scleral spur
The posterior wall of the scleral sulcus is formed by a group of fibers, parallel to the limbus that
project inward like a fibrous ring, called the scleral spur. These fibers are composed of 80%
collagen (collagen type I and III) and 5% elastic fibers. The spur is attached anteriorly to the
trabecular meshwork and posteriorly to the sclera and the longitudinal portion of the ciliary
muscle [26]. When the ciliary muscle contracts, it pulls the scleral spur posteriorly, it increases
the width of the intertrabecular spaces and prevents Schlemm`s canal from collapsing [27].
c. Ciliary body band
This is structure that is located posterior to scleral spur. When the iris inserts into the anterior
side of the ciliary body, it leaves a variable width of the latter structure visible between the iris
and scleral spur, corresponding to the ciliary body band. Gonioscopically, it appears as a
brownish band.
d. Trabecular meshwork
The aqueous humor leaves the eye at the anterior chamber angle through the conventional system
consisting of the trabecular meshwork, Schlemms canal, intrascleral channels, and episcleral
and conjunctival veins. The trabecular meshwork consists of connective tissue surrounded by
endothelium. In a meridional section, it has a triangular shape, with the apex at Schwalbes line
and the base at the scleral spur.
The meshwork consists of a stack of flattened, interconnected, perforated sheets, which run from
Schwalbes line to the scleral spur. This tissue may be divided into three portions: a) uveal
meshwork, b) corneoscleral meshwork and c) juxtacanalicular tissue6. By gonioscopy, the
trabecular meshwork can be separated into two portions: an anterior (named non-pigmented)
and a posterior (pigmented).
The inner layers of the trabecular meshwork can be observed in the anterior chamber angle and
are referred to as the uveal meshwork. This portion is adjacent to the aqueous humor, is arranged
in bands or rope-like trabeculae, and extends from the iris root and ciliary body to the peripheral
cornea. These strands are a normal variant and are called by a variety names such as iris process,
pectinated fibers, uveal trabeculae, ciliary fibers, and uveocorneal fibers. The deeper layers of the
uveoscleral meshwork are more flattened sheets with wide perforations.
The outer layers, the corneoscleral meshwork, consist of 8 to 15 perforated sheets. The
corneoscleral trabecular sheets insert into the scleral sulcus and spur. These sheets are not
visible gonioscopically. The perforations are elliptical and become progressively smaller from
the uveal meshwork to the deep layers of the corneoscleral meshwork [28]. The aqueous humor
leaves the trabecular in a tortuous route until reaching Schlemms canal, because the perforations
are not aligned.
The ultrastructure of the trabecular, uveal and corneoscleral meshworks is similar. Each sheet is
composed of four concentric layers. The trabecular beams have a central core of connective
tissue of collagen fiber types I and III and elastin. There is a layer composed of elastic fibers that
provides flexibility to the trabeculae. The core is surrounded by a glass membrane, which is
composed of fibronectin, laminin, heparin, proteoglycan and collagen type III, IV and V. The
endothelial layer is a continuous layer and covers all the trabeculae. The endothelial cells are
larger, more irregular than corneal endothelial cells. They are joined by gap junctions and tight
junctions and have microfilaments, including actin filaments and intermediate filaments
(vimentin and desmin) [30].
3. Nodul Iris (Buschka dan Koeppe)
Small nodules (granuloma) can also be seen on the iris named Berlin nodules located on the
iris base in the AC angle, Busacca nodules on the iris or Koeppe nodules on the pupillary
margin.
4. Blindness
1. Avoidable
- Cataract
- Refractive errors
- Diabetic retinopathy
- Trachoma
- Glaucoma
2. Unavoidable
- Retinal causes of childhood blindness
- ARMD
- Optic atrophy
- Amblyopia
- Phthisis/absent globe
3. Treatable
- Refractive error
- Cataract
- Uncorrected aphakia
- PCO (Posterior Capsule Opacification)
- Glaucoma
- Diabetic retinopathy
4. Untreatable
- ARMD
- Optic atrophy
2. Posterior synechiae. These are adhesions between the posterior surface of iris and
anterior capsule of crystalline lens (or any other structure which may be artificial lens,
after cataract, posterior capsule (left after extracapsular cataract extraction) or anterior
hyaloid face. These are formed due to organization of the fibrin-rich exudates.
Morphologically, posterior synechiae may be segmental, annular or total.
1. Segmental posterior synechiae refers to adhesions of iris to the lens at some points .
2. Annular posterior synechiae (ring synechiae are 360o adhesions of pupillary margin
to anterior capsule of lens. These prevent the circulation of aqueous humour from
posterior chamber to anterior chamber (seclusio pupillae). Thus, the aqueous collects
behind the iris and pushes it anteriorly (leading to iris-bombe formation) . This is
usually followed by a rise in intraocular pressure.
3. Total posterior synechiae due to plastering of total posterior surface of iris with the
anterior capsule of lens are rarely formed in acute plastic type of uveitis. These result
in deepening anterior chamber.